X-linked lymphoproliferative disease

X-linked lymphoproliferative disease (XLP) is an inherited immune defect caused by germline mutations in SH2D1A (SH2domain containing gene 1A; also known as DSHF SAP), a gene that encodes a small adaptor protein expressed in T, NK, and some B cells. The clinical features of UP are variable and include fulminant infectious mononucleosis, lymphoma, and hypogammaglobulinemia. Studies of the SH2D1A protein revealed important pathways regulating antiviral immunity. By interacting with specific cell-surface receptors, such as 2B4 (CD244), SLAM (CD150), and NTB-A, SH2D1A might regulate important aspects of immune cell function, including NK cell cytotoxicity, T-cell proliferation, and T(H)1 cytokine secretion. Abnormalities in SH2D1A amino acid composition and protein expression levels seem to cause aberrant lymphocyte activation, contributing to the dysregulated immune response that characterizes XLP.